Loeys-Dietz syndrome: Difference between revisions
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==Overview== | ==Overview== | ||
'''Loeys-Dietz syndrome''' is a recently-discovered [[autosomal dominant]] genetic [[syndrome]] which has many features similar to [[Marfan syndrome]], but which is caused by [[mutation]]s in the genes encoding [[transforming growth factor]] beta receptor 1 (''[[TGFBR1]]'') or 2 (''[[TGFBR2]]''). It is characterized by numerous site of aneurysms in the aorta (outpouchings in the weakened areas) in children <ref>{{cite journal |author=Loeys BL, Schwarze U, Holm T, ''et al'' |title=Aneurysm syndromes caused by mutations in the TGF-beta receptor |journal=N. Engl. J. Med. |volume=355 |issue=8 |pages=788-98 |year=2006 |pmid=16928994 |doi=10.1056/NEJMoa055695}}</ref><ref>{{cite journal |author=LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM |title=Severe aortic and arterial aneurysms associated with a TGFBR2 mutation |journal=Nature clinical practice. Cardiovascular medicine |volume=4 |issue=3 |pages=167-71 |year=2007 |pmid=17330129 |doi=10.1038/ncpcardio0797 |url=http://www.nature.com/ncpcardio/journal/v4/n3/full/ncpcardio0797.html}}</ref>. These aneurysms are more prone to rupture at a smaller diameter, putting the children at risk for major internal bleeding or dying if they are not detected and treated in a timely manner. | '''Loeys-Dietz syndrome''' is a recently-discovered [[autosomal dominant]] genetic [[syndrome]] which has many features similar to [[Marfan syndrome]], but which is caused by [[mutation]]s in the genes encoding [[transforming growth factor]] beta receptor 1 (''[[TGFBR1]]'') or 2 (''[[TGFBR2]]''). It is characterized by numerous site of aneurysms in the aorta (outpouchings in the weakened areas) in children <ref>{{cite journal |author=Loeys BL, Schwarze U, Holm T, ''et al'' |title=Aneurysm syndromes caused by mutations in the TGF-beta receptor |journal=N. Engl. J. Med. |volume=355 |issue=8 |pages=788-98 |year=2006 |pmid=16928994 |doi=10.1056/NEJMoa055695}}</ref><ref>{{cite journal |author=LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM |title=Severe aortic and arterial aneurysms associated with a TGFBR2 mutation |journal=Nature clinical practice. Cardiovascular medicine |volume=4 |issue=3 |pages=167-71 |year=2007 |pmid=17330129 |doi=10.1038/ncpcardio0797 |url=http://www.nature.com/ncpcardio/journal/v4/n3/full/ncpcardio0797.html}}</ref><ref>Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M,Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak Pj, Cameron DE, Backer JD, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. 2005. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat. Genet 37:275-281.</ref>. These aneurysms are more prone to rupture at a smaller diameter, putting the children at risk for major internal bleeding or dying if they are not detected and treated in a timely manner. | ||
==Historical Perspective== | ==Historical Perspective== | ||
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==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
[[Category:Cardiology]] | [[Category:Cardiology]] | ||
Revision as of 13:17, 29 October 2012
| Loeys-Dietz syndrome | |
| OMIM | 609192 |
|---|---|
| DiseasesDB | 34032 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Synonyms and keywords: Furlong's syndrome
Overview
Loeys-Dietz syndrome is a recently-discovered autosomal dominant genetic syndrome which has many features similar to Marfan syndrome, but which is caused by mutations in the genes encoding transforming growth factor beta receptor 1 (TGFBR1) or 2 (TGFBR2). It is characterized by numerous site of aneurysms in the aorta (outpouchings in the weakened areas) in children [1][2][3]. These aneurysms are more prone to rupture at a smaller diameter, putting the children at risk for major internal bleeding or dying if they are not detected and treated in a timely manner.
Historical Perspective
It was identified and characterized by American physician Harry C. Dietz and Belgian physician Bart L. Loeys, for whom it is named.
Classification
- LDS type I - Presence of craniofacial involvement
- LDS type II - Absence of craniofacial involvement
Pathophysiology
Many of the physical findings typical in Loeys-Dietz syndrome are also found in Marfan syndrome cases, including increased risk of ascending aortic aneurysm and aortic dissection:
- Abnormally long limbs and fingers
- Dural ectasia (a gradual stretching and weakening of the dura mater that can cause abdominal and leg pain).
However, it also has some additional traits not typical of Marfan patients, including widely spaced eyes, a split uvula in the back of the throat, and skin findings such as easy bruising or abnormal scars.
Diagnosis
Symptoms
The main clinical characteristics include:
- Widely spaced eyes (orbital hypertelorism)
- Cleft palate or bifid uvula (a split in the tissue that hangs down in the back of the throat)
- Aortic and arterial aneurysms/dissections with tortuosity (corkscrew structure) of the arteries.
Physical Examination
Bones and Joints
- Scoliosis
- Indented or protruding chest wall (pectus excavatum or pectus carinatum)
- Contractures of fingers and toes (camptodactyly)
- Long fingers and lax joints
- Club foot
- Premature fusion of the skull bones (craniosynostosis)
- Joint hypermobility
Skin
- Translucency of the skin with velvety texture
Neurological examination
- Abnormal junction of the brain and medulla (Arnold-Chiari malformation)
Heart
- Murmurs:
- Systolic ejection murmur: Bicuspid Aortic valves
- Machinery murmur: Congenital heart problems including patent ductus arteriosus (connection between the aorta and the lung circulation)
- Early or mid-diastolic murmur: atrial septal defect (connection between heart chambers)
Screening and Surveillance
2010 ACCF/AHA Guideline Recommendations: Diagnosis and Management of Patients with Thoracic Aortic Disease (DO NOT EDIT) [4]
Recommendations for Aortic Imaging in Genetic Syndromes
| "1. Patients with Loeys-Dietz syndrome or a confirmed genetic mutation known to predispose to aortic aneurysms and aortic dissections (TGFBR1, TGFBR2, FBN1, ACTA2, or MYH11) should undergo complete aortic imaging at initial diagnosis and 6 months thereafter to establish if enlargement is occurring. (Level of Evidence: C)" |
| "2. Patients with Loeys-Dietz syndrome should have yearly magnetic resonance imaging from the cerebrovascular circulation to the pelvis. (Level of Evidence: B)" |
Treatment
As there is no known cure, Loeys-Dietz syndrome is a lifelong condition. Due to the high risk of death from aortic aneurysm rupture, patients should be followed closely to monitor aneurysm formation, which can then be corrected with vascular surgery.
Previous research in laboratory mice has suggested that the angiotensin II receptor antagonist losartan, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A large clinical trial sponsored by the National Institutes of Health is currently underway to explore the use of losartan to prevent aneurysms in Loeys-Dietz patients.
References
- ↑ Loeys BL, Schwarze U, Holm T; et al. (2006). "Aneurysm syndromes caused by mutations in the TGF-beta receptor". N. Engl. J. Med. 355 (8): 788–98. doi:10.1056/NEJMoa055695. PMID 16928994.
- ↑ LeMaire SA, Pannu H, Tran-Fadulu V, Carter SA, Coselli JS, Milewicz DM (2007). "Severe aortic and arterial aneurysms associated with a TGFBR2 mutation". Nature clinical practice. Cardiovascular medicine. 4 (3): 167–71. doi:10.1038/ncpcardio0797. PMID 17330129.
- ↑ Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M,Holm T, Meyers J, Leitch CC, Katsanis N, Sharifi N, Xu FL, Myers LA, Spevak Pj, Cameron DE, Backer JD, Hellemans J, Chen Y, Davis EC, Webb CL, Kress W, Coucke P, Rifkin DB, De Paepe AM, Dietz HC. 2005. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat. Genet 37:275-281.
- ↑ Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE; et al. (2010). "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine". Circulation. 121 (13): e266–369. doi:10.1161/CIR.0b013e3181d4739e. PMID 20233780.